The present invention relates to compositions comprising phenyl-glycine derivatives, methods of topically applying the compositions, as well as systemic use of the compositions for various skin conditions and diseases. The phenyl-glycine derivatives include 4-hydroxyphenyl-glycine, 4-hydroxyphenyl-glycinamide, 4-hydroxyphenyl-glycine esters, N-acetyl-4-hydroxyphenyl-glycine, N-acetyl-4-hydroxyphenyl-glycinamide, N-acetyl-4-hydroxyphenyl-glycine esters, N-acetyl-4-acetoxyphenyl-glycine, N-acetyl-4-acetoxyphenyl-glycinamide, N-acetyl-4-acetoxyphenyl-glycine esters and 4-acetoxyphenyl-glycinamide.
Phenyl-glycine also is known as Phenyl-2-aminoethanoic acid. While all natural proteins are formed from about 20 common amino acids, the parent compound of the present invention, phenyl-glycine is not an amino acid found in such proteins. Phenyl-glycine compounds and compositions have been known to be useful, for example, as neurotoxic injury-reducing agents (U.S. Pat. No. 4,918,064), as photopolymerizable compound initiators (U.S. Pat. No. 6,261,544), as developing agents for photography, and for inhibiting the growth of fungi (U.S. Pat. No. 4,492,683). The disclosures of these patents are incorporated by reference herein in their entirety. These documents do not suggest the use of phenyl-glycine compounds and its derivatives for treating cosmetic disorders.
In our U.S. patent application Ser. No. 06/945,680, filed Dec. 23, 1986, entitled xe2x80x9cAdditives Enhancing Topical Actions of Therapeutic Agents,xe2x80x9d and related applications, issuing, inter alia, as U.S. Pat. Nos. 5,665,776, 5,389,677, and 5,422,370, we described and claimed compositions for and methods of enhancing the therapeutic effect of a cosmetic or pharmaceutical agent by using a hydroxyacid in combination with the agent. The disclosures of these documents are incorporated by reference herein in their entirety. The above-mentioned documents do not, however, disclose or suggest that a phenyl-glycine compound or derivative thereof would be useful for treating any skin conditions.
In our related U.S. patent application Ser. No. 07/683,437, filed Apr. 10, 1991, entitled xe2x80x9cCompositions Comprising 2-Hydroxycarboxylic Acids and Related Compounds, and Methods for Alleviating the Signs of Dermatological Aging,xe2x80x9d and related applications, and issuing, inter alia, as U.S. Pat. Nos. 5,547,988, 5,554,597, and 5,561,158, we described and claimed the use of topical compositions containing a 2-hydroxycarboxylic acid or related compound for use in alleviating or improving the signs of aging, including the signs caused by intrinsic and extrinsic aging or extrinsic factors, of the skin, hair and nails. The disclosures of these documents are incorporated by reference herein in their entirety. These documents do not disclose or suggest, however, a phenyl-glycine compound or derivative thereof, or their use in treating any skin conditions.
In our U.S. Pat. No. 6,159,485 entitled xe2x80x9cN-Acetyl Aldosamines, N-Acetylamino Acids and Related N-Acetyl Compounds and Their Topical Use,xe2x80x9d and our recent U.S. patent application No. 09/560,901, filed Apr. 28, 2000, entitled xe2x80x9cN-Acetyl Aldosamines and Related N-Acetyl Compounds, and Their Topical Use,xe2x80x9d we described and claimed the use of N-acetyl derivatives of aminosugars and amino acids for topical treatment of various skin conditions and diseases. The amino acids were based on those commonly known 20 amino acids which are found in natural proteins. Although phenylalanine is a known amino acid present in natural proteins, phenyl-glycine is not known to exist in animal proteins and this compound has not been mentioned or implied for use in treating skin conditions.
It would be desirable to develop new and useful compounds and compositions that are useful in treating various skin conditions and disorders. It also would be desirable to develop new compounds and compositions useful in treating skin changes associated with aging, such as wrinkles, lack of elasticity, decreased collagen, and the like.
It therefore is a feature of an embodiment of this invention to provide methods and compositions comprising phenyl-glycine and its derivatives that are useful in topical as well as systemic treatment and prevention of various cosmetic conditions and dermatological disorders. Examples of cosmetic conditions and dermatological disorders may include, but are not limited to, promoting wound healing, general care of skin, hair, nail, oral, vaginal and anal mucosa, oral, gum diseases, dry skin, acne, ichthyosis, psoriasis, eczema and signs of aging, changes or damage to skin, nail and hair; the signs of skin, nail and hair changes associated with intrinsic and/or extrinsic aging.
The phenyl-glycine compounds and derivatives thereof of the present invention can be represented by the following generic formula: 
wherein, R1 and R2 are independently H, I, F, Cl, Br, OH, SH, NH2, NHNH2, alkyl, aralkyl, alkoxy, acetoxy, acyloxy group having 1 to 9 carbon atoms, and being attached at the 2, 3 or 4 position of the phenyl group, whereby when R1 and/or R2 are OH, SH, NH2, they may be acetylated or acylated with 1 to 9 carbon atoms; R3 is H, formyl, acetyl, propanoyl, acyl, alkyl, aralkyl or an aryl group having 1 to 9 carbon atoms; R4 is OH, NH2, NHOH, NHNH2, or OR; where R is an alkyl, aralkyl or aryl group having 1 to 9 carbon atoms; the H attached to any carbon or nitrogen atom may be substituted by I, F, Cl, Br, OH, SH, NH2, NHNH2, an alkyl, aralkyl, alkoxy or acyl group having 1 to 9 carbon atoms. Phenyl-glycine and its derivatives may be present as isomeric D or L, non-isomeric or racemic DL, as a free acid, salt, lactone, amide or ester form.
Preferred phenyl-glycine derivatives useful in the compositions and methods of the invention preferably include 4-hydroxyphenyl-glycine, 4-hydroxyphenyl-glycinamide, 4-hydroxyphenyl-glycine methyl ester, 4-hydroxyphenyl-glycine ethyl ester, 4-hydroxyphenyl-glycine propyl ester, 4-hydroxyphenyl-glycine isopropyl ester, N-acetyl-4-hydroxyphenyl-glycine, N-acetyl-4-hydroxyphenyl-glycinamide, N-acetyl-4-hydroxyphenyl-glycine methyl ester, N-acetyl-4-hydroxyphenyl-glycine ethyl ester, N-acetyl-4-hydroxyphenyl-glycine propyl ester, N-acetyl-4-hydroxyphenyl-glycine isopropyl ester; N-acetyl-4-acetoxyphenyl-glycine, N-acetyl-4-acetoxyphenyl-glycinamide, N-acetyl-4-acetoxyphenyl-glycine methyl ester, N-acetyl-4-acetoxyphenyl-glycine ethyl ester, N-acetyl-4-acetoxyphenyl-glycine propyl ester, N-acetyl-4-acetoxyphenyl-glycine isopropyl ester and 4-acetoxyphenyl-glycinamide.
In accordance with a feature of an embodiment of the invention, there is provided a cosmetic composition that includes a therapeutically effective amount of the above-mentioned phenyl-glycine compounds and derivatives. The composition of the present invention preferably includes the above-described phenyl-glycine compounds in combination with an excipient such as a pharmaceutically, cosmetically and/or topically acceptable carrier.
In accordance with another feature of an embodiment of the present invention, there is provided a method of improving, treating, ameliorating, alleviating, or reducing any of the above-mentioned and below-described cosmetic conditions and dermatological disorders comprising topically applying an effective amount of a composition comprising a phenyl-glycine compound or derivative thereof.
These and other features of the invention will be readily apparent to those skilled in the art upon reading the detailed description that follows.